In vivo failure characteristics of human trabecular bone are fundamental to understanding osteoporosis, bone remodeling, and prosthesis design. No data is available on the failure behavior of human trabecular bone subjected to multiaxial stresses such as those that occur during trauma. The goal of this research is to provide such data in the form of experimentally-validated multiaxial failure criteria (e.g. Tsai-Wu formulated in terms of both stress and strain coupled with measures of apparent density and stereologic parameters; and empirical criteria). Such failure criteria will be applied to a number of anatomic sites and clinically relevant stress states, namely on-axis loading for the vertebral body, proximal tibia and proximal femur, and off-axis and combined axial-shear loading for the proximal femur. Two hypotheses will be tested: 1) failure of human trabecular bone is controlled primarily by the imposed strains, and, except for low-density bone that may exhibit buckling at the microstructural level, failure strains are independent of apparent density and anatomic site and depend only on how the bone is loaded; 2) multiaxial failure criteria can be established that accurately predict failure of trabecular bone under selected multiaxial stress states. Uniaxial experiments will be performed in tension, compression and shear to obtain failure properties of 180 specimens of trabecular bone, taken from the spine, femur and tibia. The uniaxial data will be used to establish the principle of strain-controlled failure of trabecular bone and predictions will be made of the multiaxial failure behavior. This will be followed by a series of biaxial and off-axis experiments on 50 additional specimens to prospectively test these predictions and validate the failure criterion. 3D stereologic measures of architecture will also be obtained from high resolution (1K x 1K) geometric models of each specimen, and this information will be used to assess the effects of architecture on multiaxial failure behavior. The information obtained from this research will have immediate application in orthopaedic research, particularly for the study of age-related hip and spine fractures where it will improve fracture risk prediction. This study will also form the basis for future research on the effects of aging, disease, drug treatment, and prosthesis implantation on the failure characteristics of human trabecular bone.